PROJECT SUMMARY/ABSTRACT This proposal details the career development plan and research project designed to develop Joseph Cheung, M.D., M.S., into an independent clinician-scientist specializing in the central nervous system hypersomnia disorders. Dr. Cheung's long term goals are to understand the genetic and neurobiological basis of hypersomnia disorders. To achieve these goals, the proposed research and career development plan will further his training in a) mastering actigraphy data analysis, b) understanding and performing genetic (exome sequence) analysis, c) becoming an expert in hypersomnia disorders. These objectives will be accomplished through a combination of didactic coursework, multidisciplinary mentorship, and research activities. His mentoring team will consist of Emmanuel Mignot M.D., Ph.D. (Sleep Genetics), Jamie Zeitzer, Ph.D. (Circadian Biology), Manuel Rivas, Ph.D. (Computational Genetics), and Ruth O'Hara, Ph.D. (Neurocognitive Disorders). This training plan will complement Dr. Cheung's background in neurology and sleep medicine, and will take place at Stanford University, which features extensive educational resources and a superb interdisciplinary environment. This research proposal aims to study idiopathic hypersomnia, a rare and disabling sleep disorder that is poorly understood at this time. Patients with idiopathic hypersomnia suffer from chronic excessive daytime sleepiness, often despite a long sleep time. The first aim of this research involves obtaining clinical and research data from idiopathic hypersomnia patients recruited from the Stanford Technology Analytics and Genomics in Sleep study (STAGES). Objective sleep duration measurements by actigraphy will be used to better characterize idiopathic hypersomnia patients with long sleep and without long sleep time. Various demographic, clinical and actigraphic characteristics between these two subtypes of idiopathic hypersomnia will be compared to yield important clinical insights into this rare sleep disorder. Furthermore, idiopathic hypersomnia patients with objectively verified long sleep time will represent the best possible hypersomnia phenotype for genetic studies. The second aim of this study will involve performing whole-exome sequencing in patients with idiopathic hypersomnia with long sleep, with a goal to identify relevant, associated genetic factors. Results from this research will have significant clinical impact by providing a deeper phenotypic characterization on idiopathic hypersomnia. Identification of genetic factors associated with long sleep hypersomnia will help elucidate the pathophysiology of idiopathic hypersomnia and basic mechanisms of human sleep regulation, leading to translational opportunities in central nervous system hypersomnia disorders. In addition, the proposed training plan will help Dr. Cheung develop into an independent physician- scientist in sleep medicine, specializing in central nervous system hypersomnia disorders and sleep genetics.